PROJECT SUMMARY/ABSTRACT Skin fibrosis, also termed skin scarring, is a significant medical problem without good treatment options. Skin fibrosis is a feature of various diseases, ranging from post-surgical scarring to traumatic injury and burns, to immune-mediated conditions including scleroderma and chronic graft versus host disease. These feature unifying pathologic findings: an increased number of fibroblasts and collagen resulting in thickened skin that results in significant functional, social and psychological morbidity. The use of light emitting diode-red light (LED-RL) is an innovative approach, as current therapeutic options for skin fibrosis are limited and demonstrate undesirable side effects, something we hope to avoid with LED-RL phototherapy. This new approach using LED-RL phototherapy has the potential to shift the treatment paradigm for skin fibrosis toward safer, less expensive, portable, home-based therapy. The specific hypothesis of this proposal is that LED-RL phototherapy can alter the clinical manifestations of surgical scarring by reduction of in vivo dermal fibroblast number and collagen, and is based upon in vitro preliminary data that demonstrates that LED-RL is anti-fibrotic at higher doses, reducing fibroblast proliferation and collagen. For ultimate patient benefit, this patient-oriented research Phase I and Phase II clinical trials aim to evaluate the safety of higher doses of visible LED-RL, and determine whether LED-RL can be used to reduce skin scarring after surgery. We will also screen for potentially novel molecular candidates modulated by LED-RL phototherapy using RNA-Seq and microRNA arrays and confirm findings using RT-PCR. Our long-term goal is to pioneer new LED-RL technology as a safer therapeutic intervention for the treatment of skin fibrosis. In the future, we hope to study the effectiveness of LED-RL to inhibit or treat scarring in patients with burns, trauma, and immune-mediated forms of skin scarring.